Processes for the preparation and purification of hydroxymethylfuraldehyde and derivatives

ABSTRACT

A method for utilizing an industrially convenient fructose source for a dehydration reaction converting a carbohydrate to a furan derivative is provided. Recovery methods also are provided. Embodiments of the methods improve upon the known methods of producing furan derivatives.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority to and incorporates by referenceU.S.Provisional Application No. 60/635,406, filed Dec. 10, 2004 and U.S.patent application Ser. No. 11/070,063, filed Mar. 2, 2005. Thisapplication is a division of co-pending U.S. application Ser. No.11/298,014, filed Dec. 9, 2005, now U.S. Pat. No. 7,317,116 which isincorporated by reference herein in its entirety.

FIELD OF THE INVENTION

Improved methods of producing chemical compounds are included herein.The dehydration reaction of common carbohydrates to form commerciallyimportant compounds, furan derivatives, and methods of optimizing thereactions to efficiently synthesize the products, as well as improvedmethods of purification are included herein.

BACKGROUND OF THE INVENTION

2,5-(Hydroxymethyl)furaldehyde, also known as2,5-(hydroxymethyl)furfural (HMF), has many important industrial andcommercial applications, largely due to its many functional groups andability to serve as a precursor in many polymerization reactions. HMF,for example, is a suitable starting source for the formation of variousfuran monomers required for the preparation of non-petroleum-derivedpolymeric materials. HMF, as well as other 2,5-disubstituted furanicderivatives, also has great potential for use in the field ofintermediate chemicals from regrowing resources. Also due to its variousfunctionalities, HMF may be used to produce a wide range of products,including, but not limited to, polymers, solvents, surfactants,pharmaceuticals, and plant protecting agents. HMF is shown in thestructure below:

The use of HMF and other furfural derivatives may be compared with theuse of corresponding benzene-based macromolecular compounds. In order tobe cost-effective and compete in this market, HMF must be able to beproduced at competitive prices. The production of HMF has been studiedfor years, but an efficient and cost-effective method of producing HMFin high yields has yet to be found. HMF is primarily produced from thedehydration reaction of a carbohydrate compound, particularlymonosaccharides, including glucose and fructose. Complications arisefrom the rehydration of HMF after the dehydration occurs, which oftenyields the by-products of levulinic acid, and formic acid. Anothercompeting side reaction is the polymerization of HMF and/or fructose toform humin polymers.

Hexoses are the preferred carbohydrate source from which HMF is formed.Fructose is the preferred hexose used for the dehydration reaction toform HMF. This is in part because fructose has been shown to be moreamendable to the dehydration reaction to a form HMF. Fructose is shownby the structures below:

Fructose however, is more expensive than other hexoses, such as glucose(dextrose), and maltose, for example. Early processes and procedures forthe production of HMF concentrated on the use of crystalline fructose,but its widespread use is prevented by its high cost. Other sources offructose, including high-fructose corn syrup (HFCS), have been used toproduce HMF and other furan derivatives. Szmant and Chundury used highfructose corn syrup as a starting material in forming HMF, as disclosedin a 1981 article in J. Chem. Tech. Biotechnol., 31, (pgs. 135-145).Szmant uses a variety of carbohydrates as starting material, but designsreaction conditions specific to each fructose source. Szmant, forexample, uses a boron trifluoride catalyst (BF₃Et₂O) with DMSO as asolvent in the conversion of HFCS to HMF, but utilizes differentcatalyst/solvent combinations with different starting materials. Use ofBF₃Et₂O as a catalyst is not economically practical since it cannot berecovered and re-used. Furthermore, Szmant requires the use of aPluronic emulsifier to suppress foaming. Szmant also requires bubblingof nitrogen to suppress oxidation. Still further, Szmant requires theuse of DMSO as a solvent, which is not easily separable from the HMFproduct, and therefore creates difficulties with product recovery. It isvery desirable, therefore, to develop an industrially practicableprocess for producing HMF in high purity.

U.S. Pat. No. 6,706,900 to Grushin et al. (Grushin '900) also disclosesthe dehydration of fructose in the form of high-fructose corn syrup, toform HMF as an intermediate; but this process is performed in thecontext of forming diformylfuran, also known as 2,5-dicarboxaldehyde(DFF). The reaction proceeds in an aqueous environment, and the HMF thatis formed is not isolated from the reaction mixture, but rather isdirectly converted to DFF without an isolation step. The reactionconditions of Grushin '900 are therefore not constrained byconsiderations of product yields of HMF, as it is formed as anintermediate that is not isolated as a product. More importantly from apractical commercial standpoint, Grushin '900 is not constrained byconsiderations of isolating HMF from the product mixture. An efficientmethod for producing HMF in desirable yields and sufficiently highpurity from a natural and industrially convenient fructose source thatmay include other mixed carbohydrates has yet to be found.

Water has in the past been used as a solvent of choice in dehydrationreactions forming HMF because of the solubility of fructose in water.Aqueous conditions, however, have proven to deleteriously affect thedehydration reaction of fructose to HMF in a variety of ways. Aqueousconditions have led to decreased yield of HMF as low selectivity for thedehydration reaction has been demonstrated. Furthermore, solvation ofprotons in water highly reduces the catalytic activity for thedehydration reaction. Low selectivity of the dehydration reactionsimultaneously leads to increased polymerization reactions and huminformation, which also interfere with the synthesis of HMF.

In an attempt to solve such problems associated with aqueous systems,one proposed solution involves an improvement by simultaneouslyextracting HMF after the dehydration reaction. A similar attempt toimprove yields involves the adsorption of HMF on activated carbon. Thekey factor in these processes is a rapid removal of HMF from the acidicmedium in which it is formed. However, these systems generally sufferfrom high dilution or partially irreversible adsorption of HMF.

In another attempt to solve the problems of aqueous systems, an organicsolvent may be added to the aqueous solution, such as, for example,butanol or dioxane. Such systems, however, present a difficulty in thatrehydration of HMF is common and ether formation of HMF occurs with thesolvent if alcohols are employed. High yields of HMF, therefore, werenot found with the addition of these organic solvents. In a furtherattempt to provide an adequate solvent system, aqueous solvent mixturesand anhydrous organic solvents have also been employed to ensurefavorable reaction conditions. Examples of anhydrous organic solventsused include dimethylformamide, acetonitrile, dimethylsulfoxide, andpolyethylene glycol.

Dimethylsulfoxide (DMSO), for example, has been extensively studied andemployed as a solvent in the dehydration reaction to form HMF. Improvedyields of HMF have been reached with ion exchangers or boron trifluorideetherate as a catalyst, and even without any catalyst. DMSO presents aproblem, however, in that recovery of HMF from the solvent is difficult.

Furthermore, although dehydration reactions performed in solvents withhigh boiling points, such as dimethylsulfoxide and dimethylformamide,have produced improved yields, the use of such solvents iscost-prohibitive, and additionally poses significant health andenvironmental risks in their use. Still further, purification of theproduct via distillation has not proven effective for a variety ofreasons. First of all, on long exposure to temperatures at which thedesired product can be distilled, HMF and impurities associated with thesynthetic mixture tend to be unstable and form tarry degradationproducts. Because of this heat instability, a falling film vacuum stillmust be used. Even in use with such an apparatus however, resinoussolids form on the heating surface causing a stalling in the rotor, andthe frequent shutdown resulting therefrom makes the operationinefficient.

Catalysts may also be used to promote the dehydration reaction. Somecommonly used catalysts include cheap inorganic acids, such as H₂SO₄,H₃PO₄, HCl, and organic acids such as oxalic acid, levulinic acid, andp-toluene sulfonic acid. These acid catalysts are utilized in dissolvedform, and as a result pose significant difficulties in theirregeneration and reuse, and in their disposal. In order to avoid theseproblems, solid sulfonic acid catalysts have also been used. Solid acidresins, however, are limited in use by the formation of deactivatinghumin polymers on their surfaces under conditions taught by others.Other catalysts, such as boron trifluoride etherate, can also be used.Metals, such as Zn, Al, Cr, Ti, Th, Zr, and V can be used as ions,salts, or complexes as catalysts. Such use has not brought improvedresults, however, as yields of HMF have continued to be low. Ionexchange catalysts have also been used, but have also delivered low HMFyields under conditions taught by others, and further limit the reactiontemperature to under 130° C.

SUMMARY OF THE INVENTION

Provided herein is an improved method of preparing2,5-(hydroxymethyl)furaldehyde comprising: i) combining a fructosesource, a solvent selected from the group consisting of1-methyl-2-pyrrolidinone, dimethylacetamide, dimethylformamide andcombinations of thereof, with a catalyst to provide a reaction mixture;ii) heating said reaction mixture to a temperature and for a timesufficient to promote an acid-catalyzed dehydration reaction of fructosein said fructose source to form a product mixture; and iii) isolating2,5-(hydroxymethyl)furaldehyde from said product mixture.

In another embodiment, there is provided a method of preparing2,5-(hydroxymethyl)furaldehyde comprising: i) combining a fructosesource, an organic solvent, and an acid catalyst to provide a reactionmixture; ii) heating said reaction mixture to a temperature and for atime sufficient to promote a dehydration reaction of fructose in saidfructose source to form a first product mixture; iii) neutralizing thepH of the first product mixture to a pH of about 7 to 9; iv) distillingthe first product mixture after neutralizing the pH to remove saidorganic solvent remaining in the first product mixture; and v) purifyingsaid product mixture to provide a second product mixture comprisinggreater than 60% by weight of 2,5-(hydroxymethyl)furaldehyde.

Also provided also herein is a method of preparing2,5-(hydroxymethyl)furaldehyde comprising the steps of: i) combining afructose source, an acid catalyst, a first organic solvent, and a secondorganic solvent that is non miscible with the first organic solvent toprovide a reaction mixture, the first and second organic solvents beingselected so that the second organic solvent preferentially dissolves2,5-(hydroxymethyl)furaldehyde relative to the first organic solvent;ii) heating said reaction mixture to a temperature and for a timesufficient to promote a dehydration reaction of fructose in saidfructose source to form a product mixture with a first immiscible phaseand a second immiscible phase; and iii) isolating2,5-(hydroxymethyl)furaldehyde from said second immiscible phase of saidproduct mixture.

In another embodiment, provided herein is a method of preparing anR-oxymethylfurfural ether of hydroxylmethylfurfural of the formula:

where R is selected from the group consisting of alkyl, cycloalkyl,allyl and aryl, comprising: (i) combining a fructose source, an R—OHsolvent, and an acid catalyst to form a reaction mixture; (ii) heatingsaid reaction mixture to a temperature and for a time sufficient topromote an acid-catalyzed dehydration reaction fructose in the fructosesource and to form R-oxymethylfurfural in a product mixture; and (iii)Isolating the R-oxymethylfurfural from said product mixture.

Also provided herein is a method of preparing levulinic acid comprising:(i) combining a fructose source, at least one of polyethylene glycol andend capped polyethylene glycol, and an acid catalyst to form a reactionmixture; (ii) heating said reaction mixture to a temperature and for atime sufficient to promote an acid-catalyzed dehydration reaction offructose in the fructose source and to form levulinic acid in a productmixture; and (iii) isolating levulinic acid from said product mixture.

In another embodiment, provided herein is a method of preparing2,5-bis-(hydroxymethyl)furan comprising: heating a reaction mixturecomprising 2,5-(hydroxymethyl)furaldehyde, a solvent, and a catalystsystem comprising nickel and zirconium at a temperature, for a time, andat a pressure sufficient to promote reduction of the2,5-(hydroxymethyl)furaldehyde to 2,5-bis-(hydroxymethyl)furan toproduce a product mixture comprising 2,5-bis-(hydroxymethyl)furan.

Provided herein is an improved method of preparing2,5-(hydroxymethyl)furaldehyde. The method includes the steps of: i)combining materials comprising a fructose source, a solvent, and acatalyst to form a reaction mixture; ii) heating said reaction mixtureto a temperature and for a time sufficient to promote an acid-catalyzeddehydration reaction of fructose in said fructose source to form aproduct mixture; and iii) isolating 2,5-(hydroxymethyl)furaldehyde fromsaid product mixture. Preferably the catalyst is a heterogeneous,re-usable, or recyclable catalyst.

In one embodiment the fructose source is high fructose corn syrup, andthe method is performed under vacuum conditions. In a further embodimentthe carbohydrate source is added gradually in a stepwise fashion oncethe reaction has been initiated, this entails the addition of two ormore discrete aliquots over a specified period of time. In an additionalembodiment, the mixed carbohydrate source comprises a first carbohydratesource in a first physical state, and a second carbohydrate source in asecond physical state, wherein the first and second physical states arenot the same, that is to say they are in different physical states.Suitable carbohydrate sources include, but are not limited to, a hexose,a pentose, fructose syrup, crystalline fructose, and, process streamsfrom the crystallization of fructose.

Suitable mixed carbohydrate source may comprise any industriallyconvenient carbohydrate sources, such as corn syrup. The mixedcarbohydrate sources include, but are not limited to, hexoses, fructosesyrup, crystalline fructose, high fructose corn syrup, crude fructose,purified fructose, high fructose corn syrup refinery intermediates andby-products, process streams from crystallizing fructose or glucose, andmolasses, such as soy molasses resulting from production of soy proteinconcentrate.

Provided also herein is a further method of preparing2,5-(hydroxymethyl)furaldehyde that includes the steps of: i) combiningmaterials comprising a carbohydrate source, an organic solvent, and anion-exchange resin catalyst to form a non-aqueous reaction mixture; ii)heating said non-aqueous reaction mixture to a temperature and for atime sufficient to promote a dehydration reaction of said carbohydratesource to form a first product mixture; iii) removing the ion-exchangeresin catalyst from the first product mixture to provide a productisolate; iv) distilling the product isolate to remove said solventremaining in said product isolate; and v) purifying said product isolateto provide a second product mixture comprising greater than 60% byweight of 2,5-(hydroxymethyl)furaldehyde. In one embodiment, the productisolate is adjusted to a neutral pH after removing the ion-exchangeresin from said product mixture, and before being subjected to adistillation to remove the organic solvent.

In one embodiment, the product mixture may be further isolated by suchmethods which are well known in the art, such as, but not limited to,filtration, vacuum or suction filtration, or gravity filtration.Purification of the product isolate may be carried out by a solventextraction process to provide the second product mixture. Examples ofsolvent extraction processes that may be used include, but are notlimited to, a column chromatography process and liquid-liquidextraction. A liquid-liquid extraction process comprises adding amixture of a water-immiscible organic solvent and water to the productisolate to form an organic phase and an aqueous phase. This is followedby recovering the organic phase, and removing the water-immisciblesolvent to yield purified 2,5-(hydroxymethyl) furaldehyde.

The possible extracting solvents include, but are not limited to, ethylacetate, methyl isobutylketone, methyl ethyl ketone, methyl t-butylether, ethyl lactate, octanol, pentanol, and butyl acetate andcombinations thereof. In a certain embodiment, the second productmixture comprises greater than 75% by weight of2,5-(hydroxymethyl)furaldehyde. Yet another embodiment, the secondproduct mixture comprises greater than 95% by weight of2,5-(hydroxymethyl)furaldehyde.

In one embodiment, after product isolation the ion-exchange resincatalyst may be rinsed with the organic solvent used to carry out thereaction to recover product contained within the resin. After the rinse,the ion-exchange resin catalyst may be reused in a subsequent reaction.In a further embodiment, after product isolation the ion-exchange resinmay be rinsed with a second organic solvent to recover product containedwith in the resin. After the rinse, the ion-exchange resin catalyst maybe reused in a subsequent reaction.

Provided also herein is a further method of preparing2,5-(hydroxymethyl)furaldehyde. The method includes: i) combiningmaterials comprising a carbohydrate source, a solvent and anion-exchange resin catalyst to form a reaction mixture; ii) heating thereaction mixture to a temperature and for a time sufficient to promote adehydration reaction of said carbohydrate source to form a first productmixture; iii) isolating the first product mixture to provide a productisolate. The method optionally comprises one or more of the followingsteps: iv) adjusting the product isolate to a neutral pH; v) adding anon-volatile flowing agent to the product isolate; vi) distilling thenon-volatile flowing agent and the product isolate to remove the solventfrom the product isolate; and vii) purifying the product isolate toprovide a second product mixture comprising greater than 75% by weightof 2,5-(hydroxymethyl)furaldehyde.

In an embodiment, the purification of the product isolate may beperformed by a process selected from the group consisting of short pathdistillation, thin film evaporation, wiped film evaporation,crystallization, and adsorption to an inert adsorbent. Adsorbentsinclude, but are not limited to, silica, carbon, alumina, and otherresins. A non-volatile flowing agent may be added to the product isolateto enhance separation. The non-volatile flowing agent may be chosen fromthe group consisting of polyethylene glycol, polyethylene glycolmonoether, polyethylene glycol diether, and combinations thereof. In afurther embodiment, the non-volatile flowing agent may be purified to are-usable form after it has performed its role in the purificationprocess. Such purification process may take place with the use of carbonas disclosed herein.

Provided also herein is a further method of preparing2,5-(hydroxymethyl)furaldehyde. The method includes: i) combiningmaterials comprising a carbohydrate source, a catalyst, a first organicsolvent, and a second organic solvent to form a non-aqueous reactionmixture wherein said first organic solvent and said second organicsolvent are immiscible in each other; ii) heating the non-aqueousreaction mixture to a temperature and for a time sufficient to promote adehydration reaction of the carbohydrate source in said first organicsolvent to form a product mixture with a first immiscible phase and asecond immiscible phase; and iii) isolating2,5-(hydroxymethyl)furaldehyde from said second immiscible phase of saidproduct mixture.

In one embodiment of the above method, the second organic solvent ischaracterized by an ability to solubilize HMF in the presence of thefirst organic solvent, which is immiscible with regard to the secondorganic solvent and HMF. The second organic solvent may be selected fromthe group including, but not limited to, methyl isobutyl ketone, ethylacetate, and chloroform. The first organic solvent is characterized asbeing less able to solubilize HMF than the second organic solvent whenin contact with the second organic solvent; the result of which is atwo-phase system. HMF is less soluble in said first immiscible organicphase than in said second immiscible organic phase. In one embodiment,the first organic solvent is dimethyl formamide.

Provided also herein is a method of preparing2,5-bis-(hydroxymethyl)furan. The method includes heating a reactionmixture comprising 2,5-(hydroxymethyl)furaldehyde, a solvent, and acatalyst system comprising nickel and zirconium at a temperature, for atime, and at a pressure sufficient to promote reduction of the2,5-(hydroxymethyl)furaldehyde to 2,5-bis-(hydroxymethyl)furan toproduce a product mixture comprising 2,5-bis-(hydroxymethyl)furan.

In one embodiment, the method provides that greater than 90% of the2,5-(hydroxymethylfuraldehyde) is converted to2,5-bis-(hydroxymethyl)furan. In another embodiment, greater than 95% ofthe 2,5-(hydroxymethylfuraldehyde) is converted to2,5-bis-(hydroxymethyl)furan, and in yet a further embodiment, greaterthan 99% of the 2,5-(hydroxymethylfuraldehyde) is converted to2,5-bis-(hydroxymethyl)furan.

In an embodiment, the method takes place with a temperature which isbetween about 125° C. and about 175° C. In another embodiment, themethod takes place with a temperature which is between about 140° C. andabout 160° C. In an embodiment, the pressure is between about 1,000pounds per square inch and about 1,400 pounds per square inch. Inanother embodiment, the pressure is between about 1050 pounds per squareinch and about 1,250 pounds per square inch.

In an embodiment, the time sufficient to promote reduction of the2,5-(hydroxymethyl)furaldehyde to 2,5-bis-(hydroxymethyl)furan is lessthan about three hours. In another embodiment, the time sufficient topromote reduction of the 2,5-(hydroxymethyl)furaldehyde to2,5-bis-(hydroxymethyl)furan is less than about two hours. In a furtherembodiment, the time sufficient to promote reduction of the2,5-(hydroxymethyl)furaldehyde to 2,5-bis-(hydroxymethyl)furan is aboutone hour.

In an embodiment, the method of preparing 2,5-bis-(hydroxymethyl)furanfurther includes isolating 2,5-bis-(hydroxymethyl)furan from the productmixture by filtration to remove the catalyst and rotary evaporation toremove the solvent. In an embodiment, the solvent is one of ethylacetate, acetate, methyl acetate, butyl acetate, isopropanol, andbutanol. In another embodiment, the reaction mixture comprising2,5-(hydroxymethyl)furaldehyde is a crude reaction mixture.

DETAILED DESCRIPTION OF THE INVENTION

Reusable or recyclable catalysts are preferred for use in the reaction,as they provide for increased efficiency, and economic and industrialfeasibility. As used herein, the term “recyclable catalyst” refers to acatalyst which is not irreversibly expended as a result of the reaction.In other words, the catalyst may be used again. Examples of recyclableor reusable catalysts include, but are not limited to, solid acidcatalysts, ion-exchange resins, zeolites, Lewis acids, clays, andmolecular sieves. Solid acid catalysts often comprise a solid materialwhich has been functionalize to impart acid groups that arecatalytically active. Solid acid catalysts may have a broad range ofcomposition, porosity, density, type of acid groups and distribution ofacid groups. Solid acid catalysts may be recovered and reused,optionally with a treatment to regenerate any activity that may havebeen lost in use. Some solid acid catalysts that may be used in thedisclosed process include, but are not limited to Amberlyst 35,Amberlyst 36, Amberlyst 15, Amberlyst 131 (Rohm and Haas, Woodridge,Ill.), Lewatit S2328, Lewatit K2431, Lewatit S2568, Lewatit K2629(Sybron Corp, Birmingham, N.J.), Dianion SK104, Dianion PK228, DianionRCP160, RCP21 H, Relite RAD/F (Mitsubishi Chemical, White Plains, N.Y.),and Dowex 50WX4 (Dow Chemical).

One example of a solvent that may be used is a polar solvent. The polarsolvent maybe a polar aprotic solvent. Examples of possible solventsinclude, but are not limited to, 1-methyl-2-pyrrolidinone,dimethylacetamide, dimethylformamide, dimethyl sulfoxide, methyl ethylketone, methyl isobutylketone, acetonitrile, propionitrile, andcombinations thereof.

In certain embodiments of the method, over 40% of hexoses present in thestarting reactants are converted to HMF, the percent conversion beingcalculated by molar yield as described below. Yield may be increased byaltering any of the variables, such as solvent type, concentration,catalyst, time and/or temperature of the reaction conditions, etc. Ithas been further found that the gradual removal of water from thedehydration reaction increases the yield of HMF. The dehydration offructose to HMF occurs with the loss of three water molecules, and theformation of three points of non-saturation, or double bonds (two alkenebonds, and the carbonyl group). By removing water as it is formed,side-reactions are thereby minimized, and an increased yield has beenobserved. Water removal may take place via evaporation. A rotaryevaporation machine may be employed to promote water removal. The use ofa rotary evaporator, or “rotovap,” is well-known in the art. Waterremoval may also be carried out by evaporation from the reaction mixtureand condensation as ice or water on a cold finger or reflux condenser.Water may also be removed by distillation, including azeotropicdistillation with a water-entraining solvent which may optionally bestripped of water and the water depleted solvent returned to thereaction vessel. A suitable distillation apparatus, such as a Barrefttype receiver may also be employed. A water-absorbing material may alsobe used to remove water. Such materials are well-known in the art, andinclude, but are not limited to, molecular sieves.

In one embodiment, the reactions disclosed herein are performed atmoderately high temperatures, typically in a range of from about 95° toabout 125° C. In a further embodiment, the temperature range is fromabout 105° C. to about 115° C. It is preferable to use temperaturesbelow 200 degrees Celsius. The reactions disclosed herein typicallyoccur in a time frame of from about one to about six hours. Moretypically, the reactions take from about two hours to about five and ahalf hours. If additional steps regarding the isolation and purificationof HMF are preformed, additional time may be required.

As used herein, the term “zeolite” refers to a hydrated silicate ofaluminum and one or both of sodium and calcium. Examples include, butare not limited to, analcite, chabazite, heulandite, natrolite,stilbite, thomsonite, in either powder or pellet form. Commercialzeolites products include, but are not limited to, CBV 3024 and CBV5534G (Zeolyst International), T-2665, T-4480 (United Catalysis, Inc),LZY 64 (Union Carbide), and H-ZSM-5 (PQ Corporation).

As used herein, Cornsweet 90 refers to a high fructose corn syrupproduct of commerce nominally containing 60% to 70% fructose. Highfructose corn syrup refinery intermediate and by-product is afructose-rich stream generated in a fractionation system positionedafter an isomerization column in the production of high fructose cornsyrup. A suitable process stream from crystallizing fructose is called“mother liquor” and comprises a solution of fructose in ethanol.Typically this process stream is about 24% solids, almost all of thesolids being fructose, and contains about 60% ethanol. For use in HMFproduction, the ethanol can be removed from the mother liquor. A similarmother liquor from glucose crystallization contains about 50% solids.Mixed carbohydrate sources can be obtained by blending carbohydrates,such as by adding crystalline fructose to high fructose corn syrup.

As used herein, “reaction yield” is calculated using the equation (molesof product/moles of starting material)*100. Product purity is reportedon a weight percent basis.

As used in this equation, “starting material” refers to the fructosepresent in the carbohydrate source, mixed carbohydrate source, or otherreactant for the particular dehydration reaction.

As used herein, the term “fructose source” refers to a material thatcomprises sucrose. Typical embodiments are solutions having at least 25%sucrose by solute weight, and which may include other materials such asother carbohydrate compounds. Preferably, the carbohydrate compounds arehexoses. The versatility of the reaction conditions provided hereinallow an industrially convenient source to be used as the startingmaterial, that is to say, the reaction is not limited to a particularcarbohydrate source or to fructose of high purity.

Suitable fructose sources typically include high fructose corn syrup(HFCS) or any HFCS refining process stream that includes at least 25%sucrose. HFCS is typically commercially available in products comprisingsolutions having 42% to 95% fructose by solute weight which aretypically sold for use as industrial scale sweeteners. The mosteconomical embodiments of the invention use HFCS having about 90%sucrose by solute weight. However, less economical embodiment'sinvention can be practiced with sources having less sucrose by weight.To improve economic efficiencies, less pure sucrose sources can beconveniently blended with higher purity sucrose sources or evencrystalline sucrose to achieve a solution having at least 25% sucrose bysolute weight.

Optional neutralization of the product isolate is carried out byaddition of a suitable alkali substance, such as a basic ion exchangeresin, potassium hydroxide, or sodium hydroxide. This neutralizationstep allows for subsequent product recovery by distillation withoutheat-catalyzed degradation or polymerization, resulting in theelimination of tarry degradation products and resinous solids beingformed in distillation. This neutralization step also allows forsubsequent product recovery with a flowing agent without heat-catalyzeddegradation or polymerization, resulting in the elimination of tarrydegradation products and resinous solids being formed in distillation.

HMF can be purified from reaction mixtures by removal of catalyst resinand forming a product isolate, neutralizing the product isolate,removing solvent from product isolate by distillation, and treating theresulting distillant with water and an organic solvent. HMF partitionsto the organic solvent and can be recovered with purity in excess of 95%by weight. This level of purity has not been obtained by otherprocesses.

After HMF has been purified from reaction mixtures by removal of thesolid acid catalyst and forming a product isolate, the solid acidcatalyst may be rinsed with the organic solvent used to carry out thereaction to recover product contained within the catalyst. After therinse, the solid acid catalyst may be reused in a subsequent reaction.In a preferred embodiment, after HMF has been purified from reactionmixtures by removal of the solid acid catalyst forming a productisolate, the solid acid catalyst may be rinsed with a second organicsolvent to recover product contained with in the catalyst. After therinse, the solid acid catalyst may be reused in a subsequent reaction.

Purity was determined by ¹³C NMR and Proton NMR, in some cases bycapillary GC, and in some cases by UV adsorption.

As used herein, the term “non-aqueous mixture” refers to a mixturecomprising a non-aqueous solvent and at least one other component,wherein the content of the solvent is greater than the content of the atleast one other component, as measured by volume. The at least one othercomponent may comprise, without limitation, a water-containingsubstrate, such as HFCS, or an organic solvent. Non-aqueous solvents areusually measured by volume, and other components are usually measured byweight.

As used herein, the term “isolate” refers to the process of preservationof a material originally present in a product mixture after the productmixture has been subjected to a step to remove other material from theproduct mixture, as well as the isolated material resulting from theprocess. Examples of “other material” that is removed includes withoutlimitation, solid material, such as catalyst by methods including, butnot limited to, the processes of filtration, decantation,centrifugation, and washing. Filtration may be performed by one of theprocesses selected from the group comprising but not limited to gravityfiltration, vacuum filtration, and suction filtration.

The term “non-volatile flowing agent” as used herein refers to an inertmaterial which, when added to a product mixture, aids in the recovery ofthe desired compound by distillation. In certain embodiments, thefugacity of the flowing agent is sufficiently low so that it will notvolatilize as the target product is removed by evaporation.

The formation of two immiscible solvent phases in the reaction mixturefacilitates purification of an HMF product. Solvents can be easilyclassified on the basis of polarity. One such measure of polarity is theLog P value. Log P is defined as the partition coefficient of a givencompound in a two-phase system of water and octanol. Log P can bedetermined experimentally or calculated from hydrophobic fragmentalconstants according to standard procedures (Hansch, C. & Leo, A (1979)Substituent constants for correlation analysis in chemistry and biology.John Wiley & Sons, New York N.Y.; Leo, A., Hansch, C. & Elkins, D.(1971) Chem. Rev. 71, 525;Rekker; R. F. (1977) The hydrophobicfragmental constant, Elsevier, Amsterdam; Rekker, R. F. & de Kort, H. M.(1979) Eur. J. Med. Chim. 14, 479).

Preferred two-phase organic solvent systems include a first solventhaving a log P value of less then zero and a second solvent having a logP value in the range of about 0.4 to about 3.4; a further two-phaseorganic solvent systems include a first solvent having a log P value inthe range of about −0.75 to about −1.95. In a further embodiment thesecond solvent has a log P value in the range of from about 0.6 to about2.7, and in an additional embodiment, the two-phase organic solventsystems include a first solvent having a log P value of about −1.04 anda second solvent having a log P value of about 1.32. A suitabletwo-phase organic solvent system comprises a first phase ofdimethylformamide and a second phase of methyl isobutyl ketone. Table 1provides Log P data for certain solvents.

Methyl isobutyl ketone is generally miscible with a broad range ofsolvents (J. S. Drury (1952) Miscibility of solvent pairs, Industrialand Engineering Chemistry 44:11, page C-684). Solvents immiscible withmethyl isobuyl ketone include diethanolamine, ethylene glycol, glyceroland trimethylene glycol. None of these solvents are suitable for theintended reaction because of their reactivity.

TABLE 1 Log P data for some solvents Solvent Log P* 1, 2-Dichlorobenzene3.38 Carbon tetrachloride 2.83 Toluene 2.69 Chloroform 2.24 Benzene 2.032-Heptanone 1.83 Butyl acetate 1.71 1,2-Dichloroethane 1.48 Methylisobutyl ketone 1.32 Dichloromethane 1.25 Ethyl propionate 1.212-Pentanone 0.91 Diethyl ether 0.89 t-Amyl alcohol 0.89 Butanol 0.88Cyclohexanone 0.81 Ethyl acetate 0.66 Pyridine 0.64 Tetrahydrofuran 0.462-Butanone 0.29 2-Propanol 0.05 Acetone −0.24 Dioxane −0.27 Ethanol−0.32 Acetonitrile −0.34 Methanol −0.77 N, N-Dimethylformamide −1.04Dimethyl sulfoxide −1.35 Formamide −1.51 Ethylene glycol −1.93 *Log Pvalues were taken from Hansch, C. & Leo, A (1979) Substituent constantsfor correlation analysis in chemistry and biology. John Wiley & Sons,New York NY; Leo, A., Hansch, C. & Elkins, D. (1971) Chem. Rev. 71, 525.

It has also been surprisingly found that other furan derivatives,particularly HMF ethers may be synthesized using the methods of thepresent invention with slight variations. Generally, ethers may beformed from any R group, such as alkyl, cycloalkyl, allyl, aryl and thelike. Such variations include but are not limited to the introduction ofalcohol having the appropriate constituent R group, such as, forexample, ethanol (EtOH) where R is C₂H₅, as a polar solvent in eitherbatch reactions or via column elution. This method would thereforecomprise: i) combining materials comprising a fructose source, analcohol solvent, and a catalyst to form a reaction mixture; ii) heatingsaid reaction mixture to a temperature and for a time sufficient topromote an acid-catalyzed dehydration reaction of the fructose in thefructose source to form a product mixture; and iii) isolating an etherderivative from said product mixture. HMF ethers, such asethoxymethylfurfural (EMF), are more stable than HMF because they lackthe exposed hydroxyl group of HMF. EMF is shown in the structure below:

In an embodiment the fructose source is a HFCS. The use of a column inthe synthetic process enables a continuous flow of heated fructosesolution, thereby decreasing the amount of polymerization and by-productformation. Further distillation may also be performed to purify EMF fromthe product mixture. The use of column elution creates a continuous flowand is a fairly simple process that efficiently leads to a more stableproduct. The subsequent purification via distillation is also a simpleprocess that is economically feasible. Furthermore, yields have beensurprisingly high, in the range of 85-100%. Purification may also beused in the form of liquid or gas chromatography.

It has also been surprisingly found that levulinic acid may beefficiently synthesized from a carbohydrate source primarily includingfructose. Levulinic acid is shown in the structure below:

The method comprises combining a fructose source, such as high-fructosecorn syrup, with a polyethylene glycol and an acidic resin to form areaction mixture. The reaction mixture is then heated with constant, orcontinuous stirring to a temperature and for a time necessary to promotethe reaction and form a product mixture. Levulinic acid is then isolatedfrom the product mixture. A polyethylene glycol block can be seen in thestructure below:

The use of end-capped polyethylene glycol material has been surprisinglyefficient as it eliminates the formation of undesirable PEG-HMF ethers.As recognized by one of ordinary skill in the art, an end-capped glycolhas the forgoing structure except that the terminal hydroxyl groups aresubstituted with an alkyl or ether group.

Another method of making levulinic acid from a fructose source involvesheating a mixture of high-fructose corn syrup and water with an acidicion exchange resin catalyst. This reaction normally proceeds in atemperature range of 100-150° C., and has surprisingly been found toproduce levulinic acid in high yields. This method provides substantialimprovement over the known method of using zeolites as catalysts insynthesizing levulinic acids.

In another embodiment, a method of preparing2,5-bis-(hydroxymethyl)furan is disclosed. The method includes heating areaction mixture comprising 2,5-(hydroxymethyl)furaldehyde, a solvent,and a catalyst system comprising nickel and zirconium at a temperature,for a time, and at a pressure sufficient to promote reduction of the2,5-(hydroxymethyl)furaldehyde to 2,5-bis-(hydroxymethyl)furan toproduce a product mixture comprising 2,5-bis-(hydroxymethyl)furan. In anembodiment, the reaction mixture comprising2,5-(hydroxymethyl)furaldehyde is a crude reaction mixture.

As used herein, the term “crude reaction mixture” refers to an unrefinedor unpurified composition.

EXAMPLES

The following are examples of the dehydration of a fructose source to afuran derivative or organic acid, as well as isolation and/orpurification techniques to optimize product recovery of increasedproduct yield. The examples are not meant to limit the scope of theinvention, as defined by the claims.

Example 1

Preparation of HMF from High Fructose Corn Syrup at 115° C. inN-Methylpyrrolidinone (NMP)

A 250 mL 3-neck round bottom flask was fitted with a magnetic stir bar,heating mantle, reflux condenser, and temperature probe. To this flaskwas charged 100 mL of NMP (Aldrich) and 20 g of Amberlyst 35 resin (Rohmand Haas, Woodridge, Ill.). Amberlyst 35 is a macroreticular, stronglyacidic, polymeric catalyst. The mixture was heated to 115° C., and 50 gof Cornsweet 90 (HFCS, ADM, Clinton Iowa) was added. Heating continuedin this manner at 115° C. over a 5 hour period. Water condensed on thereflux condenser. After 5 hours, the contents of the flask were cooledto about 70° C., and the resin removed by vacuum filtration to provide aproduct isolate. The product isolate was analyzed to provide a solutionof 14.2% HMF by weight and 4.7% fructose. Calculations indicate an 80.6%molar yield of HMF from fructose and 94.1% conversion.

Example 2

Preparation of HMF from High Fructose Corn Syrup at 105° C. in NMP

This example illustrates the effect of temperature on the dehydration offructose to HMF. A 250 mL 3-neck round bottom flask was fitted with amagnetic stir bar, heating mantle, reflux condenser, and temperatureprobe. To this flask was charged 100 mL of NMP (Aldrich) and 20 g ofAmberlyst 35 resin (Rohm and Haas, Woodridge, Ill.). The mixture wasallowed to heat to 105° C., and 50 g of Cornsweet 90 (HFCS, ADM,Clinton, Iowa) was added. Heating continued in this manner at 105° C.over a 5 hour period. Water condensed on the reflux condenser. After 5hours, the contents of the flask were cooled to about 70° C., and theresin removed by vacuum filtration to provide a product isolate. Theproduct isolate was analyzed to provide a solution of 12.9% HMF and 3.9%fructose. Calculations indicate a 71.6% molar yield of HMF from fructoseand 85.4% conversion.

Example 3

Preparation of HMF from High Fructose Corn Syrup at 105° C. in NMP UnderVacuum Conditions

This example illustrates the effect of distillation on the dehydrationof fructose to HMF. A 250 mL 3-neck round bottom flask was fitted with amagnetic stir bar, heating mantle, condenser, temperature probe, andreceiving flask. To this flask was charged 100 mL of NMP (Aldrich), 20 gof Amberlyst 35 resin (Rohm and Haas, Woodridge, Ill.), and 50 g ofCornsweet 90 syrup. The mixture was heated to 105° C. under housevacuum. The distillate was collected. After 2 hours, the contents of theflask were cooled to about 80° C., and the resin removed by vacuumfiltration to provide a product isolate. The product isolate wasanalyzed to provide a solution of 14.2% HMF and 1.1% fructose.Calculations indicate a 75.7% molar yield of HMF from fructose and 79.5%conversion.

Example 4

Preparation of HMF from High Fructose Corn Syrup at 115° C. in NMP

This example illustrates the effect of distillation on the dehydrationof fructose to HMF. A 2 L 3-neck round bottom flask was fitted with amagnetic stir bar, heating mantle, condenser, temperature probe, andreceiving flask. To this flask was added 500 mL of NMP (Aldrich), 200 gof Amberlyst 35 wet resin (Rohm and Haas, Woodridge, Ill.), and 500 g ofCornsweet 90. The mixture was heated to 115° C. and subjected to vacuumdistillation under house vacuum. After 4 hours, the resin was removed byfiltration to provide a product isolate of 729.68 g of 20.4% HMF.Calculations indicate a 68.6% yield of HMF.

Example 5

Preparation of HMF from High Fructose Corn Syrup at 105° C. in DMAc

This example illustrates the effect of solvent on the dehydration offructose to HMF. A 250 mL 3-neck round bottom flask was fitted with amagnetic stir bar, heating mantle, reflux condenser, and temperatureprobe. To this flask was charged 100 mL of DMAc (Aldrich) and 20 g ofAmberlyst 35 resin (Rohm and Haas, Woodridge, Ill.). The mixture washeated to 105° C., and 50 g of Cornsweet 90 (HFCS, ADM, Clinton, Iowa)was added. Heating was continued in this manner at 105° C. over a 5 hourperiod. Water was condensed on the reflux condenser. After 5 hours, thecontents of the flask were cooled to about 90° C., and the resin wasremoved by vacuum filtration to provide a product isolate. The productisolate was analyzed to provide a solution of 13.5% HMF and 6.0%fructose. Calculations indicate 62.1% molar yield of HMF from fructoseand 74.6% conversion.

Example 6

Preparation of EMF from Fructose in Batch Mode

A 500 mL round bottom flask equipped with a reflux condenser,temperature probe, and magnetic stir bar was charged with a solution of30 g fructose (Aldrich), 225 mL HPLC grade ethanol (Aldrich), and 30 gof Amberlyst 131 resin (Rohm and Haas). Amberlyst 131 is a stronglyacidic polymeric catalyst with a particle size of 0.7-0.8 mm and watercontent of 65%. The stirred mixture was heated to reflux for 24 hours.At this time, the slurry was filtered and the resin washed with ethanolto provide 174 mL of product isolate containing 5.4 g/L HMF and 61.6 g/LEMF.

Example 7

Preparation of EMF from Fructose via Column Elution

A 100 mL glass liquid-chromatography column (2.54 cm I.D) was slurrypacked in HPLC grade ethanol (EtOH) with Amberlyst 131 resin obtainedfrom Rohm and Haas Company (Woodridge, Ill.). The resin was washed with500 mL of EtOH. The final packed volume was 100 ml. The feed materialconsisted of 5 mL of a 20% solution of fructose in EtOH. The feed wasthen loaded on the resin column by gravity flow and fractions wereeluted. The column was maintained at 60° C. and elution at 0.6 mL/min.Table 2 summarizes the results of this study. A complete conversion offructose to a mixture of HMF/EMF was achieved, with the major productbeing EMF.

TABLE 2 Column Synthesis of EMF from Fructose using Amberlyst 131Resin.¹ Volume Fructose HMF EMF Fraction # (mL) (ppm) (ppm) (ppm) 2 8 00 0 5 13.6 0 0 0 7 21.6 0 0 294 9 32.1 262 370 1,862 11 40.1 79 4202,613 13 48.1 134 364 4,451 15 57.1 119 794 6,008 17 65.6 120 615 6,38519 73.6 0 308 4,293 21 82.1 0 0 1,488 24 94.1 0 0 276 26 102.1 0 0 60¹Column was maintained at 60° C. with a steady flow rate of 0.6 mL/min.

Example 8

Preparation of EMF from Fructose via Column Elution

This example illustrates the effect of charge in resin to Amberlyst 35obtained from Rohm and Haas Company (Woodridge, Ill.). Amberlyst 35 is amacroreticular, strongly acidic, polymeric catalyst. The feed materialwas prepared and loaded on to the column by gravity flow as described inExample 7. The column was maintained at 60° C. and the elution wascarried out at 0.6 mL/min. A summary of this is provided in table 3.Nearly 85% of the starting fructose was converted into a mixture ofHMF/EMF with the major product being EMF.

TABLE 3 Column Synthesis of EMF from Fructose using Amberlyst 35 Resin.¹Volume Fructose Ethyl HMF EMF Fraction # (mL) (ppm) Levulinate (ppm)(ppm) (ppm) 1 2.0 263 242 263 263 3 13.0 271 249 271 271 5 25.0 230 212230 230 7 34.5 253 233 253 253 8 37.5 227 209 227 579 10 46.5 2,737 9481,180 5,687 12 58.0 2,507 203 1,157 7,844 14 67.0 1,970 1,526 1,1869,526 16 76.0 520 246 325 2,023 18 85.0 282 260 282 282 19 89.5 256 236256 256 20 96.5 269 248 269 269 ¹Column was maintained at 60° C. with asteady flow rate of 0.6 mL/min.

Example 9

Process for the Synthesis and Purification of EMF

Dehydration: Amberlyst 131 Wet (145 g) was dried in vacuum at 85° C. forthree days. This catalyst was combined with 117 g crystalline fructoseand 468 g of 100% ethanol in a steel reactor. With stirring at 600 rpm,the reaction mixture was gradually heated to 110° C. over 30 minutes.The temperature was maintained for 45 minutes, and then the reactionmixture was cooled to ambient temperature over 7 minutes. The catalystwas filtered from the red-black reaction mixture, and the reactionmixture was treated with a rotary evaporator under house vacuum toremove ethanol.

Distillation of EMF on Wined-Film Evaporator: Poly(ethylene glycol)-400(47 g) was added to the dark residue (89 g). EMF was distilled from thismixture on a wiped-film evaporator at 110° C., 4.7 mm Hg, and 400 rpm,yielding a yellow distillate (68 g) containing EMF (44 g, 44% molaryield from fructose), ethyl levulinate (20 g, ELA), and ethanol (5 g).NMR (δ, 1H): 9.54, (s, 0.8 H) EMF; 7.16, (d, 1.0 H), EMF; 6.46, (s, 1.0H), EMF; 4.46, (s, 2.0 H), EMF; 4.05, (quartet, 1.0 H) ELA; 3.63,(quartet, 0.7 H), EtOH; 3.52, (quartet, 2.0 H), EMF; 2.68, (t, 1.1 H),ELA; 2.49, (t, 1.2 H), ELA; 2.12, (s, 1.6 H), ELA; 1.17, (m, 5.6 H),ELA, EMF, EtOH.

Example 10

Preparation of HMF from Fructose Using a Two-Phase Organic SolventSystem

A 500 mL round bottom three neck flask was equipped with areflux-condenser, temperature probe, and a magnetic stir bar. To thisflask was added 5 g of fructose, 5 g of Amberlyst 35 resin, and a firstorganic solvent comprising 50 mL of dimethylformamide (DMF) and a secondorganic solvent comprising 200 mL of methyl isobutyl ketone (MIBK). Thereaction was heated to 85° C. for 7 h. The mixture was cooled andfiltered. The resin was washed with small quantities of MIBK. The twolayers were separated and the product isolate (155 mL) in the MIBK phasecontained 17.9 g/L HMF to provide an overall yield of 89.3%.

Example 11

Reparation of Levulinic Acid from High Fructose Corn Syrup Using AcidicResin Catalysts

A 250 mL round bottom three neck flask was equipped with areflux-condenser, temperature probe, and a magnetic stir bar. To thisflask was added 50 g of Cornsweet 90 syrup, 20 g of Amberlyst 35 resin,and 100 mL of poly(ethyleneglycol) dimethyl ether-500. The mixture washeated to 100° C. for 4 h. The mixture was cooled and filtered toprovide an overall yield of 45.3% levulinic acid.

Example 12

Preparation of Levulinic Acid from Fructose Using Acidic Resin Catalysts

A solution of crystalline fructose (30 g, 90%) in water (500 mL) wasplaced in a 1 L autoclave reactor. To this reactor was added 60 g ofAmberlyst 35 Wet resin. The solution was stirred (500 rpm) and heated to150° C. After 4.5 hours, the reactor was cooled and the solution wasfiltered to remove the catalyst to provide a product isolate. The darkbrown product isolate (72.04 g) contained 149.83 g/kg levulinic acid toprovide an overall yield of 62% levulinic acid from fructose.

Example 13

Preparation of Levulinic Acid from High Fructose Corn Syrup Using AcidicResin Catalysts

A solution of Cornsweet 90 (45.24 g) in water (500 mL) was placed in a 1L autoclave reactor. Amberlyst 35 Wet resin (60 g) was added and themixture stirred (500 rpm). After 18 hours, the reactor was cooled andthe solution filtered to provide a product isolate. The product isolatewas treated with a rotary evaporation machine to remove the solvent, andprovided 17.98 g of dark brown oil containing 467.22 g/kg levulinic acidfor a yield of 41.2%.

Example 14

Process for the Preparation and Purification of HMF from HFCS

Step 14a. Neutralization: A 202.7 g sample of product isolate preparedas described in Example 4 was placed in a 500 mL Erlenmeyer flask, and25.0 g of poly(ethylene glycol)-600 was added to serve as a flowingagent in later purification. The mixture was stirred continuously for 30minutes at ambient temperature and neutralized with the gradual additionof Amberlyst A26OH resin (Rohm and Haas) before being subjected todistillation to remove solvent. Amberlyst A26OH is a strong base, type1, anionic, macroreticular polymeric resin. The pH of the crude productmixture was increased to 7.5-8.0 by the application of Amberlyst A26OHresin. The Amberlyst A26OH resin was then removed by filtration.

Step 14b. Distillation of DMAc: The solvent (DMAc) was distilled fromthe neutralized product mixture under vacuum (4-6 torr) at 100° C. usinga 4″ Vigreaux column with six tiers. A brown residue containing HMF andpoly(ethylene) glycol (64.5 g, 28.8% HMF) remained in the distillationvessel and 150 g of distilled DMAc were isolated.

Step 14c. Short Path Distillation of HMF: The brown residue containingHMF (145.5 g, 28.8% HMF) obtained from fractional distillation in step14b was subjected to short path distillation at 150° C. and 0.014-0.021torr. A yellow distillate (96% purity-HMF, 47.4 g) and brown residue(79.6 g) were isolated. The distillate crystallized upon cooling. NMR(δ, 1H): 9.49, (s, 1 H); 7.16, (d, 1.0 H); 6.46, (s, 1.0 H); 4.62, (s,2.0 H).

Regeneration of PEG for re-use: A 12.5 g portion of the dark brown PEGresidue obtained from the short path distillation was treated with 50 mLof hot water and 24 g of carbon (Calgon, CPG-LF 12X40). NMR indicatedthat the dark brown PEG residue was composed of greater than 95% PEG.The mixture was allowed to stir for three days. The mixture was vacuumfiltered to remove the carbon and 8.4 g of a clear yellow oil resemblingthe starting PEG in appearance was isolated. NMR indicated that thepurity of the recovered PEG was 100%.

Example 14a

Process for the Purification of HMF from HFCS

A 180 g sample of material prepared and neutralized as described inExample 4 was added to 20 g poly(ethylene glycol) dimethyl ether-500flowing agent. This material was subjected to short path distillation at150° C. and 5 mbar. A yellow distillate (67.4% purity HMF, 11.92 g) andbrown residue (191 g) were isolated.

Example 15

Process for the Purification of HMF from HFCS

Step 15a. Neutralization: An HMF product isolate as prepared in example4 was neutralized with the gradual addition of aqueous sodium hydroxide(pH 7.5) before being subjected to distillation to remove solvent.

Step 15b. Fractional Distillation to remove NMP: The neutralized productisolate was subjected to distillation under reduced pressure (4-6 torr)at 115° C. using a 4″ Vigreaux column with six tiers to remove solvent(NMP). A purified product isolate comprising a brown residue (264.6 g)and 490 g of distilled NMP were obtained.

Step 15c. Solvent Extraction: A 30.25 g sample of purified productisolate (brown residue prepared in step 15b), 45 mL of ethyl acetate,and 15 mL of water were placed in a 125 mL Erlenmeyer flask and allowedto stir at ambient temperature. After 20 min, the mixture wastransferred to a separatory funnel and the two layers separated. Theethyl acetate layer was removed and the aqueous layer was washed with 20mL of ethyl acetate, the organic layers were combined and dried overMgSO₄. The dried combined organic layer was filtered and the solventevaporated to provide 15.91 g of bright red oil which was 84.2% purityHMF.

Example 16

Process for the Purification of HMF from HFCS

Solvent Extraction: A 37.4 g sample of the solvent stripped materialprepared as described in Example 15, 47 mL of methyl isobutylketone(MIBK), and 9.6 mL of water were placed in a 125 mL Erlenmeyer flask andallowed to stir at ambient temperature. After 20 min, the solution wastransferred to a separatory funnel and the two layers separated. Theaqueous phase was washed with 20 mL of MIBK and the organic phasescombined and dried over MgSO₄. The solution was filtered and the solventevaporated to provide 24.33 g of bright red oil which was 88% purity HMFin 97% yield.

Example 17

Process for the Preparation and Purification of HMF from Fructose

Step 17a. Dehydration: Amberlyst 35 Dry (20 g) was combined with 40 gcrystalline fructose and 200 mL of acetonitrile (ACN) in a three neckflask equipped with a reflux condenser, temperature probe, and magneticstir bar. The reaction mixture was heated to flux (80° C.). Thetemperature was maintained for 5 hours, and then the reaction mixturewas cooled. The catalyst was filtered and washed with acetonitrile toprovided a product isolate. The product isolate was subjected to rotaryevaporation to provide for evaporation of the solvent and 17.6 g ofbrown oil containing 33.9% HMF.

Step 17b. Chromatographic Purification of HMF from ACN Reaction Mixture:A glass-liquid chromatography column (2.54 cm I.D) was packed in heptanewith C-Gel 560, 60-200μ silica (Uetikon, Switzerland). The feed materialfor chromatographic separation using silica gel was prepared bydissolving the dehydration product (2.95 g) in 10 mL of 80:20heptane:acetone solution. The feed material was loaded on the silicacolumn by gravity flow and fractions were eluted including those shownin Table 3.

TABLE 4 Chromatographic Purification of HMF from Crude ACN ReactionMixture.¹ Levulinic Fructose HMF Formic Acid Acid Fraction # Fructose(ppm) (ppm) (g/kg) (g/kg) 1 10 967 23,239 0.70 0.00 5 4 384 476,872 1.535.38 7 0 0 826,108 0.00 0.00 8 0 0 814,378 0.00 11.59 9 0 0 622,706 0.0017.62 10 22 2215 101,450 0.00 43.26 11 14 1386 70,241 0.00 15.22 12 131264 90,195 0.00 11.93 13 23 2252 40,207 4.03 12.14 14 28 2782 20,8177.30 8.84 15 25 2521 30,723 9.20 1.05 16 35 3457 23,024 0.00 0.00 17 585847 26,892 20.66 0.00 18 88 8799 38,819 12.46 0.00 19 128 12837 32,0508.66 0.00 20 116 11590 33,163 22.43 0.00 ¹Samples were eluted from C-Gel560, 60-200 microns using heptane: acetone gradient system.

Hence, by gradient elution of the column, isolated fractions with HMFcontent of >81% were obtained.

Example 18

Process for the Purification of HMF

A 2.0 g sample of HMF (21%) was prepared in as in the dehydration Step17a. of Example 17 using HFCS, treated with MIBK (2 mL) and water (1mL), and the layers were separated. The organic layer was dried overMgSO₄, filtered, and the solvent evaporated to provide a bright redextract of 78.9% HMF purity with 93.9% recovery of HMF from the crudematerial.

Example 19

Preparation of HMF from HFCS Using Acidic Resin Catalysts at 115° C.

This example illustrates the effect of resin on the dehydration offructose to HMF. A summary of data is shown in Table 5. A 250 mL 3-neckround bottom flask was fitted with a magnetic stir bar, heating mantle,reflux condenser, and temperature probe. To this flask was charged 50 mLof NMP (Aldrich), 50 g of polyethylene glycol dimethyl ether-600, and 50g of HFCS. The mixture was allowed to heat to 65° C., and 20 g ofDianion RCP160M resin (Mitsubishi Chemical America, Inc.) was added.Dianion RCP160M resin is a strongly acidic polymeric catalyst with aparticle size distribution of 250-710 μm and a water retention of45-55%. Heating continued in this manner at 115° C. over a 4 hourperiod. Water condensed on the reflux condenser. After 4 hours, thecontents of the flask were cooled to about 90° C., and the resin removedby vacuum filtration to provide a product isolate. The product isolatewas analyzed and found to be a solution of 17.5% HMF and 0.2% fructose.Calculations indicate 74.5% molar yield of HMF from fructose and 77.1%conversion.

TABLE 5 Comparison of HMF Conversion with Various Resins.¹ HMF YieldConversion Reference # Time (h) Resin (%) (%) 4474-58 1 RAD/F 54.1 60.12 RAD/F 63.5 67.3 4474-59 1 RCP160M 61.2 63.9 2 RCP160M 74.5 77.14474-29 1 Amberlyst 35 34.6 46.9 2 Amberlyst 35 57.1 70.2 ¹Reactionswere performed with HFCS, in NMP/PEGE at 115° C.

Example 20

Process for the Preparation and Purification of HMF from HFCS

A 10 g sample of solvent stripped material as prepared in Example 15,step 15b (42% HMF purity) was placed in 50 mL of distilled water and 10g of an inert adsorbent (Calgon CPG 12X40 carbon) was placed in a beakerand allowed to stir at room temperature for 12 hours. HMF adsorbs lightat 284 nm. UV analysis (λ=284 nm) after 12 hours of stirring indicatedHMF had been adsorbed from the mixture. The carbon was collected byfiltration, washed with water, and then allowed to stir at roomtemperature in 50 mL of acetone to desorb HMF. After 12 hours, thecarbon was removed by filtration and the filtrate evaporated to provide3.31 g of material with 80.1% HMF purity.

Example 21

Process for the Preparation and Purification of HMF from HFCS

A 33.0 g sample of solvent stripped material as prepared in Example 15(42% HMF purity) was treated with 35 g of an inert adsorbent (Calgon CPG12X40 carbon) in 165 mL of distilled water. The mixture was allowed tostir at room temperature for 12 hours. The carbon was removed by Buchnerfiltration, rinsed with water, and dried under vacuum. The dried carbonwas subjected to Soxhlet extraction using 600 mL of acetone for 18 hoursto desorb HMF. The solvent was evaporated to provide 18.41 g of deep redoil having an HMF purity of 67.1%. The total recovery of HMF was 90.1%.

Example 22

Preparation of HMF from HFCS Using Rotary Evaporation

This example illustrates the effect of rotary evaporation on thedehydration of fructose to HMF. To a 500 mL round bottom flask wascharged 100 mL of NMP (Aldrich), 25 g of high-fructose corn syrup, and15 g of wet Amberlyst 35 resin. An oil bath was heated to 120° C., andthe flask rotated in the bath, under vacuum of 200 mm Hg. Rotaryevaporation continued in this manner at 120° C. over a 1 hour period.Distillate was collected. After 1 hour, the contents of the flask weresubjected to Buchner filtration to remove the resin to provide a productisolate. The product isolate was analyzed to show 7.1% HMF, 91.5% NMP,and 1.9% water. Calculations indicate 88.6% molar yield of HMF from HFCSand 90.7% conversion.

Example 23

Preparation of HMF from HFCS with Molecular Sieves

This example illustrates the usefulness of molecular sieves as dryingagents in the production of HMF from HFCS. To a 3-neck 500 round bottomflask equipped with a condenser, temperature probe, and stirring bar,was added 100 mL of NMP, 50 g of HFCS, 20 g of wet Amberlyst 35 resin,and 20 g of UOP 3A molecular sieves. The reaction was heated to 105° C.and let stir under these conditions for 1 hour. Results indicate a 10.6%HMF solution providing an overall yield of 60.6%. The addition of sievesto promote the removal of water during the reaction allows for a fasterconversion of HFCS to HMF.

Example 24

Preparation of HMF with Gradual Addition of HFCS to Reaction Mixture

This example illustrates the effect of gradual addition of HFCS to aheated reaction mixture. A 3-neck 500 mL round bottom flask was fittedwith a dropping funnel, temperature probe, and a jacketed condenser withdistilling head. To this flask was added 100 mL of NMP and 40 g of wetAmberlyst 35 resin. The flask was heated to 130° C. with vacuum and thefeed material (100 g of HFCS in 50 mL of NMP) was added dropwise over1.5 hours. Upon complete addition of the feed, the reaction continuedwith vigorous stirring for 3 hours. At this time, the reaction wascooled to 90° C., and the resin removed via Buchner filtration (#415 VWRpaper) to provide a product isolate. Results indicate a product isolateof 10.4% HMF, 85.4% NMP, and 2.76% water. Thus, a 77.8% molar yield ofHMF was obtained.

Example 25

Preparation of 2,5-bis-(hydroxymethyl)furan (FDM) from Crude HMFReaction Mixture

The sample of HMF material (30.01 g, 66% HMF) was placed in a 1 L Parrreactor vessel with ethyl acetate (350 mL) and 2.0 g of G-69B. G-69B isa powdered catalyst obtained from Sud-Chemie, Louisville, Ky.,containing nominally 62% Nickel on Kieselguhr, with a Zirconiumpromoter, and has an average particle size of 10-14 microns. The vesselwas purged 3×500 psi hydrogen with vigorous stirring (1000 rpm). Thepressure was then maintained at 1250-1050 psi with heating to 150° C.for 1 hour. The reaction was allowed to cool and the catalyst removed byfiltration. The solvent was removed by rotary evaporation to provide27.32 g of brown liquid that solidified on cooling. TLC analysisindicated the complete conversion of HMF to FDM. ¹H NMR data reveal ahigh purity product (>90%). The overall yield of FDM from HMF is 100%.GC/MS data revealed complete conversion of HMF to FDM m/z=128, 111, 97.

Example 26

Preparation of 2,5-bis-(hydroxymethyl)furan (FDM) from Crude HMFReaction Mixture

The sample of HMF material (46.09 g, 45% HMF) was placed in a 1 L Parrreactor vessel with ethyl acetate (350 mL) and 6.15 g of G-69B. Thevessel was purged 3×500 psi hydrogen with vigorous stirring (1000 rpm).The pressure was then maintained at 1350 psi with heating to 150° C. for1 hour. The reaction was allowed to cool and the catalyst removed byfiltration. The solvent was removed by rotary evaporation to provide18.48 g of brown solid. ¹H NMR and gc/ms data reveal a high purityproduct (>95%). The overall yield of FDM from HMF is 90%. NMR (δ, 1 H):4.54 (s, 2.0 H); 6.20 (s, 1.0 H).

1. A method of preparing an R-oxymethylfurfural ether ofhydroxylmethylfurfural of the formula:

where R is selected from the group consisting of alkyl, cycloalkyl, andallyl, comprising: combining a fructose source and an R-OH solvent toform a reaction mixture and contacting the reaction mixture with a solidacid catalyst bed in a chromatographic column; heating the reactionmixture in the chromatographic column to a temperature and for a timesufficient to promote an acid-catalyzed dehydration reaction of fructosein the fructose source and to form R-oxymethylfurfural in a productmixture in the column; and simultaneously chromatographically separatingthe product mixture in the column to at least partially separate theR-oxymethylfurfural from other components of the product mixture andelute an enriched fraction containing the R-oxymethylfurfural from thecolumn.
 2. The method of claim 1 wherein the R-OH solvent is ethanol andthe R-oxymethylfurfural is ethoxymethylfurfural.
 3. The method of claim1 wherein the acid catalyst is an acidic ion exchange resin.
 4. Themethod of claim 1 wherein the fructose source is a mixed fructosesource.
 5. The method of claim 1 wherein the method further includesdistilling the enriched fraction to further purify theR-oxymethylfurfural.
 6. The method of claim 1, wherein the yield of theR-oxymethylfurfural is in the range of 85-100%.
 7. The method of claim 1wherein the reaction mixture consists essentially of the fructose sourceand the R-OH solvent in contact with the solid acid catalyst.
 8. Themethod of claim 1 wherein the column is eluted with the R-OH solvent ofthe reaction mixture.
 9. The method of claim 1 wherein the reactionmixture consists essentially of the fructose source and the R-OH solventin contact with the solid acid catalyst and the column is eluted withthe R-OH solvent of the reaction mixture.